This research addresses an important public need, the protection of an estimated 10 million workers in the U.S. who rely heavily on their voice as a primary tool of trade. Evidence has been growing that occupational voice users, such as teachers, telephone workers, ministers, counselors, interviewers, are at risk for vocal injury because they get inadequate recovery times from prolonged speaking. The underlying hypothesis is that there is a limited vibration dose that vocal fold tissues can withstand. As for hand-transmitted vibration in power tools use, a safe dose is governed by frequency, amplitude, and duration of vibration exposure. Microphone use solves the overdose problem related to vocal loudness, but does not address the problem of excessive duration. A voice dosimeter has been designed, tested, and is currently in use by teachers in the Denver area public school system to measure vocal dose. The teachers also self-monitor their vocal fatigue levels. In this renewal application, the primary focus will be on the molecular underpinnings of tissue response to excessive vibration. Specific aims are to (1) determine the ideal geometric and viscoelastic properties of the lamina propria, (2) quantify voice recovery times and relate them to auto-perceptive ratings, (3) culture distinct cell types at various states of differentiation, (4) determine the relative merits of co-culture for in vitro monolayer systems, (5) engineer a 3D in vitro model of the lamina propria in a bioreactor, (6) identify and functionally characterize candidate vibration-responsive genes, (7) develop a theoretical model of economic voice production, and (8) explore two types of economy-based vocal therapy. The ultimate goal is to provide heavy voice users with safety criteria based on genetic disposition to vocal injury, degree of training in economic voice use, accumulated dose of vibration in a typical work day, and the amount of recovery available at night and on weekends. A multi-disciplinary research team has been assembled to address this public health concern at physical, biochemical, molecular, and behavioral levels of investigation.